Identification of a novel LDLR p.Glu179Met variant in Thai families with familial hypercholesterolemia and response to treatment with PCSK9 inhibitor.

Familial hypercholesterolemia (FH) is a genetic disease characterized by elevated LDL-C levels. In this study, two FH probands and 9 family members from two families from northeastern Thailand were tested for LDLR, APOB, and PCSK9 variants by whole-exome sequencing, PCR-HRM, and Sanger sequencing. In silico analysis of LDLR was performed to analyse its structure‒function relationship. A novel variant of LDLR (c.535_536delinsAT, p.Glu179Met) was detected in proband 1 and proband 2 in homozygous and heterozygous forms, respectively. A total of 6 of 9 family members were heterozygous for LDLR p.Glu179Met variant. Compared with proband 2, proband 1 had higher baseline TC and LDL-C levels and a poorer response to lipid-lowering therapy combined with a PCSK9 inhibitor. Multiple sequence alignment showed that LDLR p.Glu179Met was located in a fully conserved region. Homology modelling demonstrated that LDLR p.Glu179Met variant lost one H-bond and a negative charge. In conclusion, a novel LDLR p.Glu179Met variant was identified for the first time in Thai FH patients. This was also the first report of homozygous FH patient in Thailand. Our findings may expand the knowledge of FH-causing variants in Thai population, which is beneficial for cascade screening, genetic counselling, and FH management to prevent coronary artery disease.

The prevalence and treatment patterns of familial hypercholesterolemia among Thai patients with premature coronary artery disease.

OBJECTIVES: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder that is characterized by severe hypercholesterolemia. The prevalence of FH in Thailand has not been reported. Therefore, this study aimed to investigate the prevalence of FH and treatment patterns among Thai patients with premature coronary artery disease (pCAD). METHODS: A total of 1,180 pCAD patients at two heart centers from northeastern and southern Thailand between October 2018 and September 2020 were enrolled. FH was diagnosed using the Dutch Lipid Clinic Network (DLCN) criteria. pCAD was diagnosed in men aged < 55 years and women aged < 60 years. RESULTS: The prevalence of definite/probable FH, possible FH, and unlikely FH in pCAD patients was 1.36% (n = 16), 24.83% (n = 293), and 73.81% (n = 871), respectively. Definite/probable FH in pCAD patients had a significantly higher frequency of STEMI but a lower frequency of hypertension than those with unlikely FH. After discharge, most pCAD patients (95.51%) received statin therapy. Definite/probable FH patients had a higher frequency of high-intensity statin therapy than those with possible FH and unlikely FH. After follow-up for 3-6 months, approximately 54.72% of pCAD patients with DLCN scores ≥ 5 had a reduction in LDL-C > 50% from baseline. CONCLUSIONS: The prevalence of definite/probable FH, particularly possible FH, was high among pCAD patients in this study. The early diagnosis of FH among Thai pCAD patients should be performed for the early treatment and prevention of CAD.

Association of CELSR2, APOB100, ABCG5/8, LDLR, and APOE polymorphisms and their genetic risks with lipids among the Thai subjects.

Background: Hypercholesterolemia is a common cardiovascular risk factor. The aim of this study was to investigate the association of CELSR2 (rs629301), APOB100 (rs1367117), ABCG5/8 (rs6544713), LDLR (rs6511720), and APOE (rs429358, rs7412) polymorphisms, and their genetic risk scores with lipids among Thai subjects. Methods: A total of 459 study subjects (184 males, and 275 females) were enrolled. Blood pressure, serum lipids, and fasting blood sugar were measured. CELSR2 (rs629301), APOB100 (rs1367117), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms were analyzed using PCR-HRM. APOE (rs429358, rs7412) polymorphism was analyzed using PCR-RFLP. Results: Total cholesterol (TC) levels were significantly higher in APOB100 AA genotype compared with GG, or AA + AG genotypes in total subjects. In addition, significantly higher concentrations of TC and low density lipoprotein cholesterol (LDL-C) were observed in APOE4 carriers compared to APOE2 carriers in total subjects, males, and females. The significantly higher concentrations of TC were observed in APOE4 carriers compared to APOE3 carriers in females. Moreover, the concentrations of TC, and LDL-C were significantly increased with genetic risk scores of APOB100, and APOE polymorphisms in total subjects, and females. There was no association between CELSR2 (rs629301), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms and serum lipids. Conclusion: APOB100 (rs1367117), and APOE (rs429358, rs7412) but not CELSR2 (rs629301), ABCG5/8 (rs6544713), and LDLR (rs6511720) polymorphisms were associated with serum lipids. The cumulative risk alleles of APOB100 (rs1367117), and APOE (rs429358, rs7412) polymorphisms could enhance the elevated concentrations of TC, and LDL-C, and they may be used to predict severity of hypercholesterolemia among Thai subjects.

Effect and correlation of patent vascular access flow on left ventricular hypertrophy in kidney transplant patients.

Background: Patency of vascular accesses (VA) is associated with left ventricular hypertrophy (LVH) in kidney transplant recipients (KTR). This level of VA flow (VAF) as related to LVH was assessed and an upward level of VA flow recommended for VA closure determined. This recommendation has not been previously reported. Methods: 123 KTR cohort patients were enrolled between August 2016 and December 2017 and their LVH and LV mass index (LVMI) by echocardiography and VAF by Doppler ultrasound were evaluated at baseline and for a 24-month follow-up period. Associations between VAF and LVH were adjusted for other factors. Results: Patients with patent VA (55.3%) had significantly greater LVH (47.1 vs. 29.1%, an adjusted odds ratio 2.44, p = 0.03) and LVMI (112.15 ± 34.4 vs. 97.55 ± 23.55 g/m2, p = 0.009) when compared with the non-VA group. A positive correlation between VAF rate and LVM was noted (r = 0.40, p < 0.001). Subgroup analysis revealed the VAF ≥ 900 ml/min had risks of LVH 3.61, and 2.86 times compared with the non-VA group and the VAF < 900 ml/min group. After a 24-month follow up, there was no significantly individual change in LVMI in patients with or without VA except 6 patients who lost their VA patency during follow-up time had a significant reduction of LVMI (120.17 ± 52.13 to 80.89 ± 22.72 g/m2, p = 0.046). Conclusions: Patency of VA in post-KT patients was associated with LVH. There was a significant reduction of LMVI after loss of VA patency. Patients with stable kidney graft function should be considered for VA closure especially if VAF is ≥ 900 ml/min.

Efficacy and safety of inhaled nitrite in addition to sildenafil in thalassemia patients with pulmonary hypertension: A 12-week randomized, double-blind placebo-controlled clinical trial.

Pulmonary hypertension is a significant complication in thalassemia patients. Recent studies showed that inhaled nebulized nitrite could rapidly decrease pulmonary artery pressure. We conducted a multicenter, randomized, double-blind, placebo-controlled trial in thalassemia patients with symptomatic pulmonary hypertension diagnosed by right heart catheterization. Eleven patients were recruited; five were assigned to the nitrite group and six to the placebo group. Patients were treated with the optimal doses of sildenafil for pulmonary hypertension and randomly assigned into the placebo or nitrite groups. Patients in the nitrite group were given inhaled nebulized 30 mg sodium nitrite twice a day for 12 weeks. The clinical outcomes measured at week 12 were the changes in 6-min walk distance (6MWD), mean pulmonary artery pressure (MPAP), and N-terminal pro B-type natriuretic peptide. The MPAP estimated by echocardiography was significantly reduced from 33.6 ± 7.5 mmHg to 25.8 ± 6.0 mmHg (mean difference = 7.76 ± 3.69 mmHg, p = 0.009 by paired t-test). Furthermore, 6MWD was slightly increased from 382.0 ± 54.0 m to 432 ± 53.9 m (mean difference = 50.0 ± 42.8 m, p = 0.059 by paired t-test) in the nitrite group. At week 12, the nitrite group had lower MPAP than the placebo group (25.8 ± 6.0 vs. 45.7 ± 18.5 mmHg, p = 0.048 by unpaired t-test). No significant difference in 6MWD and N-terminal pro B-type natriuretic peptide between the two groups was observed at week 12. There was no hypotension or other significant adverse effects in the nitrite group.

Clinical Outcomes of Asymptomatic Cardiac Involvement in Systemic Sclerosis Patients After a 2-Year Follow-Up (Extended Study).

BACKGROUND: Asymptomatic cardiac involvement in systemic sclerosis (SSc) has been reported. Long-term follow-up might elucidate the clinical implications of these abnormalities. The aim was to identify the clinical outcomes of asymptomatic cardiac involvement in SSc patients after 2 years of follow-up. METHODS: A cohort study was done at Khon Kaen University, Thailand, on adult patients with SSc who completed the preliminary study. Repeated investigations included electrocardiography, chest radiography, echocardiography, and blood tests for creatine kinase-MB, high sensitivity cardiac troponin-T, and N-terminal prohormone of brain natriuretic peptide. RESULTS: Seventy-four of the 103 patients from the previous study were enrolled. The mean duration of follow-up was 3.1 ± 0.9 years. Five patients developed symptomatic cardiac involvement-all of whom had pulmonary arterial hypertension (PAH). The incidence of symptomatic cardiac involvement for the combined 315 person-years was 1.6 per 100-person-years (95%CI 0.7-3.4). Fourteen patients died resulting in a mortality incidence of 4.4 per 100-person-years (95%CI 4.3-5.4). Persistent cardiac involvement was found in 35 patients for an incidence of 11.1 per 100-person-years (95%CI 8.0-15.5). Two of the patients who had persistent elevated cardiac enzyme developed PAH at a respective 3.7 and 39.4 months after the initial evaluation. None of the clinical parameters were predictive of symptomatic and persistent cardiac involvement. Only male sex was associated with mortality (hazard ratio 3.70; 95%CI 1.22-11.11). CONCLUSIONS: Cardiac involvement in SSc can progress slowly or even be reversed. Based on a previous test, the incidence of symptomatic cardiac involvement after 2 years was low despite its being a persistent involvement. If symptomatic cardiac involvement develops, PAH is the most prevalent symptom.

Associated factors of early-onset pulmonary hypertension and clinical difference between early- and late-onset pulmonary hypertension in Thai systemic sclerosis.

OBJECTIVES: Pulmonary hypertension (PH) is a major cause of death in systemic sclerosis (SSc). Detection of early-onset PH and its associated factors would be helpful for improving patient care. Our aims were to determine the factors associated with early-onset PH and to define the differences between early- and late-onset PH among SSc patients. METHODS: A cohort study was conducted of 409 adult SSc patients who had followed-up between January 2014 and December 2016. Early-PH is defined when the onset of PH is diagnosed within 5 years of the disease. Logistic regression analysis was applied to determine the factors associated with early-PH. RESULTS: In 3409 person-years, we diagnosed 50 cases with PH confirmation by right heart catheterization, of whom 26 were early-PH (incidence 0.7 per 100 person-years; 95%CI:0.5-1.1). Among SSc with early-PH, 69.2% had the diffuse cutaneous SSc subset and the most common PH classification was PH due to interstitial lung disease (18 cases;69.2%). According to a logistic regression analysis, early-PH was associated with a WHO functional class (WHO-FC) II and higher, cardiomegaly according to chest radiography, and tricuspid regurgitation jet maximum velocity (TRVmax)>2.8 m/s with the respective OR of 20.12 (95%CI:1.59-255.35), 7.42 (95%CI:1.35-40.88), and 8.20 (95%CI:1.17-57.64). To contrast, early-PH had a negative association with gastrointestinal involvement (OR 0.08; 95%CI:0.01-0.56). CONCLUSIONS: Early-PH is prevalent among SSc patients and the most common cause is interstitial lung disease. A poor WHO-FC, cardiomegaly, and a high TRVmax are associated with early-PH. Gastrointestinal involvement is a protective factor for early-PH in SSc.

Correlation Between N-Terminal Pro-Brain Natriuretic Peptide Levels and Cardiopulmonary Exercise Testing in Patients With Pre-Capillary Pulmonary Hypertension: A Pilot Study.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (CPET) are useful for severity assessment in patients with pulmonary hypertension (PH). Correlations between these tests in pre-capillary PH patients is less well studied. METHODS: We studied 23 patients with pre-capillary PH: 8 with idiopathic pulmonary arterial hypertension (IPAH), 6 with systemic sclerosis-associated PAH (SSc-PAH), and 9 with chronic thromboembolic pulmonary hypertension (CTEPH). Clinical evaluation, NT-proBNP levels, six-minute walking test (6MWT), spirometry, and CPET were evaluated on the same day. Correlation between NT-proBNP levels and CPET parameters were investigated. RESULTS: In all patients, NT-proBNP levels were significantly correlated with peak oxygen uptake (VO2) (r = -0.47), peak oxygen pulse (r = -0.43), peak cardiac output (CO) (r = -0.57), peak end-tidal partial pressure of carbon dioxide (PETCO2) (r = -0.74), ventilatory equivalent to carbon dioxide (VE/VCO2) at anaerobic threshold (AT) (r = 0.73), and VE/VCO2 slope (r = 0.64). Significant correlations between NT-proBNP levels and peak PETCO2 and VE/VCO2 were found in IPAH and CTEPH subgroups, and a significant correlation between NT-proBNP levels and VO2 at AT was found in the CTEPH subgroup. No significant correlation was found in the SSc-PAH subgroup. CONCLUSION: NT-proBNP levels were significantly correlated with CPET parameters in patients with IPAH and CTEPH subgroups, but not in SSc-PAH subgroup. A further study with larger population is required to confirm these preliminary findings.

Association of Major Histocompatibility Complex Class I Related Chain A/B Positive Microparticles with Acute Myocardial Infarction and Disease Severity.

BACKGROUND: Various cell types undergo activation and stress during atherosclerosis resulting in the development of acute myocardial infarction (AMI) in coronary artery disease (CAD). Major histocompatibility complex class I related chain A and B (MICA/B) can be expressed on the surface of activated and stressed cells and released into blood circulation in several forms including microparticles (MICA/B+ MPs) from various cell types. We aimed to investigate the association of these MICA/B+ MPs with the presence of AMI. Fifty-one AMI and 46 age-matched control subjects were recruited. METHODS: Levels of MICA/B+ MPs derived from various parent cells including endothelial cells, platelets, monocytes, neutrophils, and T lymphocytes were determined by flow cytometry. RESULTS: The levels and proportion of MICA/B+ MPs from all types of cell origin were significantly increased in AMI patients compared to those of the controls. A multivariate regression model showed an independent association between MICA/B+ MPs and AMI (OR = 11.6; 95% CI = 2.8, 47.3). Interestingly, based on the disease severity, we found that the levels of MICA/B+ MPs were significantly elevated in the ST-segment elevation myocardial infarction (STEMI) compared to the non-STEMI (NSTEMI) patients. Moreover, an independent association of MICA/B+ MPs with the occurrence of STEMI was also demonstrated (OR = 4.1; 95% CI = 1.5, 16.7). CONCLUSIONS: These results suggest that MICA/B+ MPs are associated with AMI and disease severity. They may act as mediators contributing to the pathological process of AMI. Alternatively, they are the results of various cell activations contributing to AMI.

Interaction of CYP2C19 G681A polymorphism and omeprazole on clopidogrel responsiveness and impact in patients with acute coronary syndrome.

OBJECTIVE: The aim of this study was to explore the individual effects of the CYP2C19 G681A polymorphism and omeprazole use and their interaction on clopidogrel responsiveness in acute coronary syndrome (ACS). The CYP2C19 G681A polymorphism and omeprazole use were both known for retarding the effects of clopidogrel under broad cardiovascular conditions; however, data from ACS patients were limited. METHODS: We conducted a cross-sectional study of 102 ACS patients who received clopidogrel before percutaneous coronary intervention. The platelet function was assessed by a Platelet Function Analyzer-200, in which clopidogrel hyporesponsiveness was defined as a closure time (CT) of ≤ 106 s. The CYP2C19 G681A polymorphism was investigated using the PCR-RFLP technique. Statistical analysis was performed by using χ test, Student's t-test, binary logistic regression, and receiver-operating characteristic (ROC) curve. RESULTS: Carriages of the CYP2C19 681A allele and omeprazole use were present in 47.1 and 37.3% patients, respectively. The mean CT ± SD was 103.1 ± 1.7 s and the prevalence of clopidogrel hyporesponsiveness was 66.7%. The CT was significantly shorter in carriages of the 681A allele compared with the 681G allele (P = 0.002), but had no significant difference in patients with vs. without omeprazole use (P = 0.467). The ROC analysis of an effect on clopidogrel hyporesponsiveness of CYP2C19 G681A alone and combination with omeprazole use had area under the curve values of 0.654 and 0.672, respectively. CONCLUSION: In ACS patients, the effect of the CYP2C19 G681A polymorphism on clopidogrel responsiveness, but not omeprazole use, is strong. However, a combination of both factors enhances clopidogrel hyporesponsiveness.

Clinical Outcomes of Myocarditis after Moderate-Dose Steroid Therapy in Systemic Sclerosis: A Pilot Study.

BACKGROUND: Myocarditis is reported in systemic sclerosis (SSc); however, treatment options and outcomes are limited. Our objective was to define cardiac outcomes after moderate-dose steroid therapy in SSc patients with myocarditis. METHOD: An open-label study was conducted among SSc patients with myocarditis-as defined by cardiovascular magnetic resonance (CMR), disease onset <5 years, and a NYHA functional class ≥II. All enrolled patients received prednisolone (30 mg/d) which would be tapered off by week 24, and CMR was followed up at the end of treatment. RESULTS: A total of 20 SSc patients were enrolled which 12 patients completed the study. At week 24, 8 of the 12 cases experienced improvement of myocarditis. Compared to those with no improvement, these 8 patients had significantly longer disease duration (p = 0.03), higher heart rate at baseline (p = 0.049) and week 24 (p = 0.04), lower left ventricular (LV) and right ventricular (RV) stroke volume at baseline (p = 0.002 and p = 0.01) and week 24 (p = 0.01 and p = 0.02), and lower LV and RV cardiac output at week 24 (p = 0.01 and p = 0.01). Four cases died during follow-up (3 due to cardiac complications, 1 due to renal crisis). The two who died from heart failure had very high NT-prohormone-brain natriuretic peptide (NT-proBNP) and impaired LV ejection fraction (LVEF), and the one who died from arrhythmia had very high sensitivity of cardiac Troponin-T (hs-cTnT). CONCLUSIONS: Moderate-dose steroid therapy may improve myocarditis in SSc. A proportion of patients died due to cardiac complications during treatment, particularly those with high hs-cTnT, high NT-proBNP, and impaired LVEF. This trial is registered with NCT03607071.

Clinical and laboratory predictions of myocardial inflammation as detected by cardiac magnetic resonance imaging in patients with systemic sclerosis: A pilot study.

BACKGROUND: Cardiac magnetic resonance imaging (cardiac MRI) has high sensitivity and specificity for differentiating cardiac fibrosis from inflammation. There is no data on the clinical and laboratory association or prediction of myocardial inflammation in systemic sclerosis-a major organ involvement in systemic sclerosis (SSc). OBJECTIVES: Our aim was to ascertain the clinical and laboratory associations with myocardial inflammation in SSc patients as detected by cardiac MRI. METHODS: A cross-sectional study was conducted among Thai adult SSc patients who had: disease onset <4 years; a New York Heart Association functional class ≥ II; and followed up at the Scleroderma Clinic, Khon Kaen University, between June 2018 and January 2019. We excluded patients who were taking steroids and/or immunosuppressants or had a diagnosed heart disease before being diagnosed with SSc. All enrolled patients underwent cardiac MRI, and clinical and laboratory assessments the same date. Myocardial inflammation was defined by cardiac MRI per the Lake Louise Criteria. RESULTS: A total of 30 SSc patients were enrolled. The female-to-male ratio was 1.8:1. The majority (73%) had diffuse cutaneous SSc. The respective mean age and median duration of disease was 57 ± 8 and 2.0 years (interquartile range 1.5-2.7). Myocardial inflammation was detected in 22 patients (73.3%). The multivariate analysis revealed that every 5 years of increased age at onset and every 5-point increase in the modified Rodnan skin score (mRSS) at onset was significantly associated with myocardial inflammation (odds ratio 0.47, 95% CI 0.22-0.98; and 2.64 95% CI 1.04-6.74, respectively). Neither the SSc subset, internal organ involvement, inflammatory markers, nor cardiac and muscle enzymes were associated with myocardial inflammation in SSc. CONCLUSION: Myocardial inflammation is common in early-onset SSc. An increased risk of myocardial inflammation was associated with young age and high mRSS at onset. Cardiac MRI is the suggested evaluation for high-risk SSc patients experiencing dyspnea on exertion.

Corynebacterium diphtheriae Native Aortic Valve Endocarditis in a Patient With Prosthetic Mitral Valve: A Rare Presentation.

Infective endocarditis due to non-toxigenic Corynebacterium diphtheriae is uncommon. We describe the case of a 42-year-old male with a history of mitral valve replacement with prosthetic valve for 4 years. He presented with fever, weight loss, dyspnea on exertion and orthopnea. The echocardiography demonstrated large vegetation attached on the left coronary cusp of the aortic valve with moderately severe aortic regurgitation but sparing of the prosthetic mitral valve. Three separate blood cultures grew Corynebacterium species. The patient underwent aortic valve replacement due to valvular dysfunction and congestive heart failure. C. diphtheriae DNA was detected by 16 S rDNA polymerase chain reaction (PCR) from the heart valve tissue. The patient recovered completely with combine antibiotics and surgical intervention. He was discharged from the hospital with good clinical outcome.

Relationship between Peripheral Arterial Stiffness and Estimated Pulmonary Pressure by Echocardiography in Systemic Sclerosis.

BACKGROUND: Pulmonary hypertension (PH) is an important lethal manifestation of systemic sclerosis (SSc). Evidence of an association between peripheral and pulmonary arterial vasculopathy in SSc has been demonstrated. We hypothesized that peripheral arterial stiffness could predict PH in SSc. METHODS: We performed a cross-sectional study among patients with SSc who underwent Cardio-Ankle Vascular Index (CAVI, VaSera VS-1000; Fukuda Denshi, Tokyo, Japan) and transthoracic echocardiography (TTE) examination to evaluate peripheral arterial stiffness and PH, respectively. The correlation between CAVI score and PH hemodynamics [right ventricular systolic pressure (RVSP) and tricuspid regurgitation velocity (TRV)] was studied. RESULTS: A total of 145 patients underwent both CAVI and TTE evaluation. The mean (standard deviation, SD) patient age was 51.5 (12.3) years; female patients constituted 72% of the subjects. Diffuse SSc occurred in 75% of the cases. The mean (SD) CAVI score was 7.6 (0.9), and the mean (SD) RVSP was 29.9 (11.2) mmHg. Correlation coefficient (r) between CAVI score and RVSP in overall, limited, and diffuse SSc were 0.107 (p = 0.200), 0.040 (p = 0.815), and 0.194 (p = 0.043), respectively. CAVI scores were borderline or abnormal (≥ 8) in 30.3% of subjects. PH was classified intermediate or high probability (TRVmax ≥ 2.9 m/s) in 19.3% of the subjects. Among the overall population, the odds ratios (95% CI) of CAVI score ≥ 8 for TRVmax ≥ 2.9 m/s in univariate and multivariate analysis were 1.23 (0.46-3.21, p = 0.678), and 0.54 (0.10-2.84, p = 0.471), respectively. CONCLUSIONS: Peripheral arterial stiffness, as measured by CAVI, has a correlation trend with the level of pulmonary arterial pressure assessed by TTE, specifically in the diffuse SSc subgroup.

The impact of non-genetic and genetic factors on a stable warfarin dose in Thai patients.

PURPOSE: The aim of this study was to investigate the contributions of non-genetic and genetic factors on the variability of stable warfarin doses in Thai patients. METHODS: A total of 250 Thai patients with stable warfarin doses were enrolled in the study. Demographics and clinical data, e.g., age, body mass index, indications for warfarin and concomitant medications, were documented. Four single nucleotide polymorphisms in the VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622, and UGT1A1 rs887829 genes were detected from gDNA using TaqMan allelic discrimination assays. RESULTS: The patients with variant genotypes of VKORC1 - 1639G > A required significantly lower warfarin stable weekly doses (SWDs) than those with wild-type genotype (p < 0.001). Similarly, the patients with CYP2C9*3 variant allele required significantly lower warfarin SWDs than those with homozygous wild-type (p = 0.006). In contrast, there were no significant differences in the SWDs between the patients who carried variant alleles of CYP4F2 rs2108622 and UGT1A1 rs887829 as compared to wild-type allele carriers. Multivariate analysis, however, showed that CYP4F2 rs2108622 TT genotype accounted for a modest part of warfarin dose variability (1.2%). In contrast, VKORC1 - 1639G > A, CYP2C9*3, CYP4F2 rs2108622 genotypes and non-genetic factors accounted for 51.3% of dose variability. CONCLUSIONS: VKORC1 - 1639G > A, CYP2C9*3, and CYP4F2 rs2108622 polymorphisms together with age, body mass index, antiplatelet drug use, amiodarone use, and current smoker status explained 51.3% of individual variability in stable warfarin doses. In contrast, the UGT1A1 rs887829 polymorphism did not contribute to dose variability.

Kussmaul's sign and rapid X-Y descents in constrictive pericarditis.

Right-sided heart failure is not uncommon. A careful jugular venous examination looking for the distinct Kussmaul's sign and rapid X-Y descents, which are highly indicative of constrictive pericarditis, is markedly helpful in guiding the correct diagnosis and proper management.

Prognostic factors of in-hospital mortality in all comers with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention.

BACKGROUND: The prognostic factors of in-hospital mortality in all comers and unselected patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) have not been well established. OBJECTIVE: To identify the predictive factors of in-hospital mortality in patients with STEMI undergoing primary PCI in a tertiary heart centre. METHODS: Between January 2008 and December 2011, all patients with STEMI undergoing primary PCI were retrospectively included in this study. Baseline characteristics and angiographic data were reviewed and recorded. The study endpoint was all-cause in-hospital mortality. RESULTS: Of the 541 patients included in the study, 63 (11.6%) died during hospitalisation. Cardiogenic shock at admission was recorded in 301 patients (55.6%) and 424 patients (78%) had multivessel disease. Median door-to-device time was 65 min. After adjustment for baseline variables, the factors associated with in-hospital mortality included age >60 years (OR 2.98, 95% CI 1.17 to 7.05; p=0.01), left ventricular ejection fraction <40% (OR 2.53, 95% CI 1.20 to 5.36; p=0.02), and final TIMI flow grade 0/1 (OR 20.55, 95% CI 3.49 to 120.94; p=0.001). CONCLUSIONS: Age, left ventricular function and final TIMI flow are significant predictors of adverse outcomes in unselected patients with STEMI undergoing primary PCI.

First Case of Tricuspid Valve Endocarditis Caused by Gemella bergeri.

Gemella bergeri is a Gram-positive cocci species arranged in pairs and composes the normal flora of oral cavity, digestive and urinary tract. Several species of Gemella are known to cause endocarditis. Here, we report the first case in Thailand of G. bergeri endocarditis whose blood culture was negative using routine methods but was positive by PCR identification of bacteria in the affected valve. A 37-year-old male presented with prolonged fever, weight loss, and dyspnea on exertion. By transthoracic echocardiography, he was suspected of having infective endocarditis of the tricuspid valve. The patient underwent tricuspid valve repair and vegetectomy. Routine hospital blood cultures were negative but G. bergeri was identified by PCR/sequencing of the heart valve tissue.

Asymptomatic cardiac involvement in Thai systemic sclerosis: prevalence and clinical correlations with non-cardiac manifestations (preliminary report).

OBJECTIVE: To determine the prevalence of asymptomatic cardiac involvement and its correlation with non-cardiac manifestation in Thai SSc patients. METHODS: A cross-sectional study was carried out between January 2012 and June 2013 at Srinagarind Hospital, Khon Kaen University, Thailand, on adult SSc patients without signs or symptoms suggestive of cardiac involvement. We excluded those with overlap syndrome, having serum creatinine >123.8 µmol/l, history of cardiac diseases, any atherosclerosis risk factors and receiving angiotensin-converting enzyme inhibitors. Non-invasive tests related to cardiac involvement were performed, including: echocardiography, ECG, chest X-ray, inflammatory biomarkers, cardiac enzymes and N-terminal prohormone of brain natriuretic peptide. RESULTS: A total of 103 SSc patients were enrolled, 61.2% of whom were in the subset. Of these, 63 patients had at least one test abnormality (prevalence 61.2%; 95% CI 51.6, 70.7). The two leading cardiac abnormalities were diastolic dysfunction (44.7%) and elevation of cardiac enzymes (36.9%). The only predictor for cardiac involvement per multivariate analysis was the dcSSc subtype with a higher modified Rodnan skin score, and shorter disease duration (odds ratio = 3.37; 95% CI 1.07, 10.65). Compared with the limited subtype, dcSSc was also significantly associated with elevated cardiac enzyme and prolonged distance between a Q wave and T wave in an ECG (QT interval). CONCLUSION: Asymptomatic cardiac involvement in Thai SSc was not uncommon, and the most common finding was diastolic dysfunction. Elevated cardiac enzymes were found in one-third of the patients, which correlated with the dcSSc subtype with a higher modified Rodnan skin score and shorter disease duration, suggestive of early myocardial microcirculation disruption. Long-term follow-up was performed to elucidate the clinical implication of these abnormalities.